p53 nuclear expression correlates with hemizygous TP53 deletion and predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with lenalidomide.

del(17p13)(TP53) seems to be an independent poor prognostic factor in patients with relapsed/refractory multiple myeloma (MM) receiving lenalidomide. However, whether aberrant p53 nuclear expression detected by immunohistochemical analysis can be used as a surrogate marker for del(17p13)(TP53) in prognostic evaluation of lenalidomide-treated relapsed/refractory MM remains unclear. The p53 expression in myeloma cells from 88 patients was evaluated by immunohistochemical analysis, and 17p13(TP53) gene status was examined by fluorescence in situ hybridization (FISH).

Cyclin kinase subunit 1B nuclear expression predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with bortezomib.

Amplification of cyclin kinase subunit 1B gene on chromosome 1q21 resulting in overexpression of cyclin kinase subunit 1B has been associated with disease progression in multiple myeloma. Bortezomib is a proteasome inhibitor that induces apoptosis in various cancer cells and has been shown to be effective as a salvage therapy for relapsed/refractory multiple myeloma. Our group has recently reported the adverse effect of 1q21 gains in relapsed and refractory multiple myeloma treated with bortezomib.

Analysis of chromosome 12p deletion in plasma cell dyscrasias.

The prognostic relevance of 12p deletion is controversial in multiple myeloma (MM) and the status of 12p deletion is unknown in other plasma cell disorders. We investigated 12p deletion in 88 patients with MM, 19 patients with monoclonal gammopathy of undetermined significance (MGUS), and 17 patients with plasma cell leukemia (PCL). Cytoplasmic immunoglobulin light chain immunofluorescence with simultaneous FISH analysis (cIg-FISH) detected hemizygous 12p deletion in 8% of MM and 24% of PCL, respectively, but in none of the MGUS cases (p=0.

Genomic aberrations and survival of patients with light-chain-only multiple myeloma undergoing autologous stem cell transplantation.

The majority of patients with multiple myeloma (MM) have intact immunoglobulin, but in a subset of patients (∼15%), their tumors produce monoclonal light chains only (LCO). Although specific genomic aberrations have emerged as a major prognostic factor in MM, their incidence and prognostic impact on LCO myeloma patients are not clear. We therefore investigated a cohort of 86 LCO MM cases diagnosed and treated with autologous stem cell transplantation at our institution.

Impact of genomic aberrations including chromosome 1 abnormalities on the outcome of patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone.

Previous literature suggests that cytogenetics may be used for risk-adapted therapy in patients with relapsed/refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone. However, the significance of each abnormality is still unclear, and chromosome 1 abnormalities have yet to be studied in this population. We therefore evaluated genetic risk factors including chromosome 1q gain and 1p loss by cIg-FISH in 143 patients with relapsed/refractory MM treated with lenalidomide and dexamethasone, and correlated the genomic aberrations with patient clinical outcomes.

CKS1B nuclear expression is inversely correlated with p27Kip1 expression and is predictive of an adverse survival in patients with multiple myeloma.

Background: CKS1B is a member of the highly conserved cyclin kinase subunit 1 (CKS1) family that interacts with cyclin-dependent kinases and plays an important role in cell cycle progression. We and others have shown that CKS1B amplification located on chromosome 1q21 is an adverse prognostic factor in multiple myeloma, but its relationship with CKS1B nuclear protein expression, is unclear. The aim of this study was to correlate nuclear CKS1B protein immunoreactivity, 1q21 amplification status, p27(Kip1) expression and survival in patients with newly-diagnosed multiple myeloma.

Aberrant nuclear p53 expression predicts hemizygous 17p (TP53) deletion in chronic lymphocytic leukemia.

Hemizygous TP53 gene deletion is the most important adverse risk factor in chronic lymphocytic leukemia (CLL), but its relationship with p53 protein expression is unclear. We investigated 110 CLL cases and correlated nuclear p53 protein immunoreactivity with TP53 gene deletion status and other CLL-associated genetic risk factors. Fluorescence in situ hybridization detected hemizygous TP53 deletions in 15 cases (13.

Cytoplasmic expression of nucleophosmin accurately predicts mutation in the nucleophosmin gene in patients with acute myeloid leukemia and normal karyotype.

Mutations in the nucleophosmin (NPM1) exon 12 resulting in delocalization of NPM1 into the cytoplasm occur in 50% to 60% of acute myeloid leukemia cases with a normal karyotype (AML-NK). As recent studies suggest such patients have a favorable prognosis and there are discordant reports of the immunohistochemical detection of cytoplasmic NPM1 (NPMc+) for predicting NPM1 gene mutations, we correlated the immunohistochemical detection of NPMc+, NPM1 gene mutations, and prognosis in 57 cases of AML-NK. All 31 NPMc+ cases (54% of total) had NPM1 mutations, but none of the 26 nucleus-restricted (NPMc-) cases (46% of total) had NPM1 mutations (P < .

Prognostic relevance of 6q deletion in Waldenström's macroglobulinemia: a multicenter study.

The deletion of the long arm of chromosome 6 is the most common cytogenetic abnormality in Waldenstrom's macroglobulinemia (WM), but its prognostic significance is unclear. We investigated 77 patients with WM by interphase cytoplasmic immunoglobulin M fluorescence in situ hybridization (cIgM-FISH) and correlated the 6q status with the patients' clinical features and survival. cIg-FISH detected hemizygous 6q deletions in 32 patients (41.

Aberrant nuclear p53 protein expression detected by immunohistochemistry is associated with hemizygous P53 deletion and poor survival for multiple myeloma.

Hemizygous TP53 deletion is an adverse risk factor in multiple myeloma (MM) but its relationship with p53 protein expression is unclear. We investigated 105 newly diagnosed myeloma patients and correlated nuclear p53 protein immunoreactivity with TP53 deletion status, myeloma-associated genetic risk factors and survival. Fluorescence in situ hybridisation (FISH) detected hemizygous TP53 deletions in 13 (12%) patients while immunohistochemistry detected nuclear p53 protein expression in 12 (11%).

p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation.

We investigated the relevance of p53 deletions to the clinical outcome of patients with multiple myeloma (MM) treated with high-dose chemotherapy and autologous stem cell transplantation. Hemizygous p53 gene deletions were detected by fluorescence in situ hybridization in 10 of 105 (9.5%) patients studied.